ArticleScience (New York, N.Y.)2021
Haplotype-resolved diverse human genomes and integrated analysis of structural variation.
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Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 499 papers.
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499citing papers in PubMed
104.6field-weighted citation impact, top 1% of its field
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Who cites it
499 citing papers in PubMed, 776 citations in OpenAlex.
- A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.Genome medicine · 2026Trial
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- Structural Variants in the Human Genome Associated With Gut Microbiome and Blood Metabolic Traits With Potential Causal Links.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Resolving missing human polymorphic inversions and other complex variants from ultralong read data.Genome research · 2026Article
- dicast: a machine learning method for accurate structural variant detection from short-read sequencing data.Genome biology · 2026Article
- Point mutations and complex variants impact gene expression and addiction-related behaviors in Heterogeneous Stock rats.bioRxiv : the preprint server for biology · 2026Article
- Structural Variant benchmarking frameworks: Parameterization, matching logic, and evaluation assumptions presented through HG002 and NA12878.PLoS computational biology · 2026Article
- TandemTwister: scalable genotyping and advanced visualization of tandem repeats.NAR genomics and bioinformatics · 2026Article
- Protocol for haplotype-resolved structural variant detection via long-read sequencing using cuteHap.STAR protocols · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
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- Structural variants contribute substantially to complex trait heritability.Research square · 2026Article
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- Population-scale disease-associated tandem repeat analysis reveals locus and ancestry-specific insights.Nature communications · 2026Article
- HPRC2: A human pangenome reference with near-complete coverage of common genetic variation.bioRxiv : the preprint server for biology · 2026Article
- Integrated SNP and SV Analyses Reveal Genetic Mechanisms Underlying High-Altitude Adaptation in Goats.Animals : an open access journal from MDPI · 2026Article
- Computational strategies for copy number variation detection, disease association, and beyond.Genome biology · 2026Review
- Diagnostic utility of clinical genome reanalysis in rare pediatric disorders using long-read sequencing.HGG advances · 2026Article
- Complex structural variation, phylogeny, and disease associations of the mucin pangenome.medRxiv : the preprint server for health sciences · 2026Article
- Pangenome-based structural variant imputation enables large-scale genotype-phenotype studies in dairy cattle.Nature communications · 2026Article
439 more citing papers are in PubMed but not listed here.
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Authors and funding
65 authors at 20 institutions in 6 countries.
Peter Ebert *Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany.ORCID https://orcid.org/0000-0001-7441-532X
Peter A Audano *Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0002-5187-0415
Qihui Zhu *The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA.ORCID https://orcid.org/0000-0003-2401-8443
Bernardo Rodriguez-Martin *European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0003-4693-3140
David PorubskyDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0001-8414-8966
Marc Jan BonderEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0002-8431-3180
Arvis SulovariDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0003-4354-9020
Jana EblerHeinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany.ORCID https://orcid.org/0000-0002-0382-3702
Weichen ZhouDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.ORCID https://orcid.org/0000-0003-4755-1072
Rebecca Serra MariHeinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany.ORCID https://orcid.org/0000-0002-2812-9653
Feyza YilmazThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA.ORCID https://orcid.org/0000-0001-8795-5800
Xuefang ZhaoCenter for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0003-4036-9577
PingHsun HsiehDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0001-8294-6227
Joyce LeeBionano Genomics, San Diego, CA 92121, USA.ORCID https://orcid.org/0000-0002-3492-1102
Sushant KumarProgram in Computational Biology and Bioinformatics, Yale University, BASS 432 and 437, 266 Whitney Avenue, New Haven, CT 06520, USA.ORCID https://orcid.org/0000-0002-2294-3988
Jiadong LinSchool of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.ORCID https://orcid.org/0000-0002-8116-5901
Tobias RauschEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0001-5773-5620
Yu ChenDepartment of Genetics and Informatics Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID https://orcid.org/0000-0002-2037-7337
Jingwen RenDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Martin SantamarinaGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Wolfram HöpsEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Hufsah AshrafHeinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany.
Nelson T ChuangInstitute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA.
Xiaofei YangSchool of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.ORCID https://orcid.org/0000-0002-5118-7755
Katherine M MunsonDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0001-8413-6498
Alexandra P LewisDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0002-6195-4786
Susan FairleyEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID https://orcid.org/0000-0001-9425-0788
Luke J TallonInstitute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA.ORCID https://orcid.org/0000-0002-4656-4480
Wayne E ClarkeNew York Genome Center, New York, NY 10013, USA.
Anna O BasileNew York Genome Center, New York, NY 10013, USA.ORCID https://orcid.org/0000-0001-5112-5880
Marta Byrska-BishopNew York Genome Center, New York, NY 10013, USA.ORCID https://orcid.org/0000-0002-9118-1032
André CorveloNew York Genome Center, New York, NY 10013, USA.ORCID https://orcid.org/0000-0003-0989-7806
Uday S EvaniNew York Genome Center, New York, NY 10013, USA.
Tsung-Yu LuDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.ORCID https://orcid.org/0000-0001-7110-3937
Mark J P ChaissonDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Junjie ChenDepartment of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA.ORCID https://orcid.org/0000-0002-0483-303X
Chong LiDepartment of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA.
Harrison BrandCenter for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.
Aaron M WengerPacific Biosciences of California, Menlo Park, CA 94025, USA.ORCID https://orcid.org/0000-0003-1183-0432
Maryam GhareghaniMax Planck Institute for Informatics, Saarland Informatics Campus E1.4, 66123 Saarbrücken, Germany.
William T HarveyDepartment of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA.ORCID https://orcid.org/0000-0003-0646-7528
Benjamin RaederEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0002-9494-8884
Patrick HasenfeldEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0003-2319-2482
Allison A RegierDepartment of Medicine, Washington University, St. Louis, MO 63108, USA.ORCID https://orcid.org/0000-0002-1932-8714
Haley J AbelDepartment of Medicine, Washington University, St. Louis, MO 63108, USA.
Ira M HallDepartment of Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.ORCID https://orcid.org/0000-0003-4442-6655
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.ORCID https://orcid.org/0000-0002-3897-7955
Oliver StegleEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0002-8818-7193
Mark B GersteinProgram in Computational Biology and Bioinformatics, Yale University, BASS 432 and 437, 266 Whitney Avenue, New Haven, CT 06520, USA.ORCID https://orcid.org/0000-0002-9746-3719
Jose M C TubioGenomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.ORCID https://orcid.org/0000-0003-3540-2459
Zepeng MuGenetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL 60637, USA.ORCID https://orcid.org/0000-0002-7717-3247
Yang I LiSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.ORCID https://orcid.org/0000-0002-0736-251X
Xinghua ShiDepartment of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA.
Alex R HastieBionano Genomics, San Diego, CA 92121, USA.ORCID https://orcid.org/0000-0001-5829-2649
Kai YeSchool of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.ORCID https://orcid.org/0000-0002-2851-6741
Zechen ChongDepartment of Genetics and Informatics Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID https://orcid.org/0000-0001-5750-1808
Ashley D SandersEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.ORCID https://orcid.org/0000-0003-3945-0677
Michael C ZodyNew York Genome Center, New York, NY 10013, USA.ORCID https://orcid.org/0000-0001-6594-7199
Michael E TalkowskiCenter for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.ORCID https://orcid.org/0000-0003-2889-0992
Ryan E MillsDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.ORCID https://orcid.org/0000-0003-3425-6998
Scott E DevineInstitute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA.ORCID https://orcid.org/0000-0001-7629-8331
Charles Lee *The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.ORCID https://orcid.org/0000-0001-7317-6662
Jan O Korbel *European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.ORCID https://orcid.org/0000-0002-2798-3794
Tobias Marschall *Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.ORCID https://orcid.org/0000-0002-9376-1030
Evan E Eichler *Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.ORCID https://orcid.org/0000-0002-8246-4014
University of Washington · USEuropean Molecular Biology Laboratory · DENew York Genome Center · USHeinrich Heine University Düsseldorf · DEBroad Institute · USEuropean Bioinformatics Institute · GBTemple University · USUniversity of Maryland, Baltimore · USUniversity of Southern California · USYale University · USBioNano Genomics (United States) · USGerman Cancer Research Center · DEJackson Laboratory · USUniversidade de Santiago de Compostela · ESUniversity of Alabama at Birmingham · USUniversity of Chicago · USWashington University in St. Louis · USWashtenaw Community College · USXi'an Jiaotong University · CNEwha Womans University · KR
Funding
NHLBI Data Stage Coordinating CenterOT3HL147154 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ashok Kumar Krishnamurthy · 2018 to 2026
$98.9MShared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Madeleine Joy Braun · 1985 to 2026
$61.9MNew York Center for Collaborative Research In Common Disease Genomics: Genome Aggregation and Joint Variant Calling for CCDG Freeze2UM1HG008901 · NHGRI · NEW YORK GENOME CENTER · PI MANIATIS, THOMAS P, WIGLER, MICHAEL H · 2016 to 2020
$56.6MINTERDISCIPLINARY TRAINING IN GENOMIC SCIENCEST32HG000035 · NHGRI · UNIVERSITY OF WASHINGTON · PI Bruce Colston Trapnell · 1995 to 2026
$24.2MIdentifying and Characterizing the Full Spectrum of Haplotype-resolved Structural Variation in Human GenomesU24HG007497 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Evan Eichler, Jan Oliver Korbel · 2019 to 2026
$17.2MSequence and Assembly of Segmental DuplicationsR01HG002385 · NHGRI · UNIVERSITY OF WASHINGTON · PI Evan Eichler · 2001 to 2026
$13.3MResearch Training in Gastroenterology and HepatologyT32DK067872 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI RAUFMAN, JEAN-PIERRE · 2005 to 2024
$7.2MClinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2MScalable tool and comprehensive maps to interpret structural variation across the neuropsychiatric spectrumR01MH115957 · NIMH · BROAD INSTITUTE, INC. · PI TALKOWSKI, MICHAEL E · 2019 to 2025
$5.4MSequence-resolved structural variation of human genomesR01HG010169 · NHGRI · UNIVERSITY OF WASHINGTON · PI Evan Eichler · 2018 to 2026
$4.5MNatural Genetic Variation in the Human GenomeR01HG002898 · NHGRI · UNIVERSITY OF MARYLAND BALTIMORE · PI DEVINE, SCOTT E · 2004 to 2019
$3.7MStructural variation analysis with and without a reference genomeR35GM138212 · NIGMS · UNIVERSITY OF VIRGINIA · PI Zechen Chong · 2020 to 2026
$2.6MEuropean Research Council 773026NCI NIH HHS P30 CA034196NHGRI NIH HHS K99 HG011041NHGRI NIH HHS R01 HG002385NHGRI NIH HHS R01 HG002898NHGRI NIH HHS R01 HG007068NHGRI NIH HHS R01 HG010169NHGRI NIH HHS R15 HG009565NHGRI NIH HHS T32 HG000035NHGRI NIH HHS U01 HG010973NHGRI NIH HHS U24 HG007497NHGRI NIH HHS UM1 HG008901NHLBI NIH HHS OT3 HL147154NICHD NIH HHS R01 HD081256NIDDK NIH HHS T32 DK067872NIGMS NIH HHS R35 GM138212NIMH NIH HHS R01 MH115957Wellcome Trust
Abstract
Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic variation, even across complex loci. We identified 107,590 structural variants (SVs), of which 68% were not discovered with short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterized 130 of the most active mobile element source elements and found that 63% of all SVs arise through homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.
Indexed as
Genetic VariationGenome, HumanHaplotypesFemaleGenotypeHigh-Throughput Nucleotide SequencingHumansINDEL MutationInterspersed Repetitive SequencesMalePopulation GroupsQuantitative Trait LociRetroelementsSequence Analysis, DNASequence InversionWhole Genome SequencingRetroelements
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